This is a competing renewal of a Program Project Grant, currently in its 16th year, which focuses on the[unreadable] molecular regulation of lung development. The program has been highly successful in bringing together an[unreadable] interactive multidisciplinary team of investigators to explore this theme, and has resulted in significant[unreadable] contributions to the field. This renewal consists of four interactive projects to study determinants of cell fate[unreadable] and differentiation in the developing lung. These projects address critical and poorly understood issues on[unreadable] the mechanisms of establishment of lung cell lineages, and on how this relates to morphogenesis and[unreadable] acquisition of differentiated cellular phenotypes.[unreadable] Project 1 addresses questions related to how the initial respiratory lineages are spatially organized and[unreadable] expanded during early morphogenesis, and the role of Notch and Fgfs in this process. Project 2 will focus on[unreadable] the mechanisms by which endogenous microRNAs control dynamic gene activity during proximal-distal[unreadable] specification of the lung. Project 3 develops new tools exploring a mouse ES cell culture system to study the[unreadable] genetic mechanisms that control early lung lineage specification. Project 4 focuses on mechanisms of[unreadable] chromatin remodeling and DMA methylation in the regulation of gene transcription during early lung[unreadable] development.[unreadable] Besides these projects, three cores are proposed. The "Administrative Core" will deal with the overall[unreadable] management and financial aspects of the Program. The "Microscopy-Image Analysis and FACS Core" will[unreadable] provide resources for histology, analysis of gene/protein expression by standard or confocal microscopy and[unreadable] for cell sorting. The "Mouse Core" will support the investigators in maintaining the various existing mouse[unreadable] lines, breeding, genotyping, and for designing constructs of new mouse lines.[unreadable] The projects and cores are designed to be highly interactive, with extensive sharing of expertise, reagents[unreadable] and model systems. Results from these studies will provide relevant insights into mechanisms of lung[unreadable] development and stem cell biology